In many circumstances, it is beneficial for an implanted medical device to release a bioactive material into the body once the device has been implanted. Such released bioactive materials can enhance the treatment offered by the implantable medical device, facilitate recovery in the implanted area and lessen the local physiological trauma associated with the implant. One type of device that has benefited from the inclusion of bioactive materials is stents. Stents are ridged, or semi-ridged, tubular scaffoldings that are deployed within the lumen (inner tubular space) of a vessel or duct during angioplasty or related procedures intended to restore patency (openness) to vessel or duct lumens. Stents generally are left within the lumen of a vessel or duct after angioplasty or a related procedure to reduce the risks of reclosure and restenosis, or re-occlusion. Including bioactive materials such as, for example and without limitation, rapamycin or paclitaxel on the surface of the implanted stent further helps to prevent restenosis.
One challenge in the field of implantable medical devices has been adhering bioactive materials to the surfaces of implantable devices so that the bioactive materials will be released once the device is implanted. One approach has been to include the bioactive materials in polymeric coatings. Polymeric coatings can hold bioactive materials onto the surface of implantable medical devices and release the bioactive materials via degradation of the polymer or diffusion into liquid or tissue (in this case the polymer is non-degradable). Degradable and non-degradable polymers such as polylactic acid, polyglycolic acid, and polymethylmethacrylate have been used in drug-eluting stents.
While polymeric coatings can be used to adhere bioactive materials to implanted medical devices, there are a number of problems associated with their use. First, it is difficult to predict the degradation kinetics of polymers. Consequently, it is difficult to predict how quickly a bioactive material in a polymeric coating will be released. If a drug releases from the polymeric coating too quickly or too slowly, the intended therapeutic effect may not be achieved. Second, in some cases, polymeric coatings produce pro-thrombotic and pro-inflammatory responses. These pro-thrombotic and pro-inflammatory effects lead to the necessity of prolonged antiplatelet therapies. Further, in the case of stents, these effects can exacerbate restenosis, a negative effect stents are designed to prevent. Third, adherence of a polymeric coating to a substantially different substrate, such as a stent's metallic substrate, is difficult due to differing characteristics of the materials (such as differing thermal expansion properties). The difficulty in adhering the two different material types often leads to inadequate bonding between the medical device and the overlying polymeric coating which can result in the separation of the materials over time. Such separation is an exceptionally undesirable property in an implanted medical device. Fourth, it is difficult to evenly coat a medical device with a polymeric coating. The uneven coating of a medical device can lead to unequal drug delivery across different portions of the device. This drawback is especially apparent in relation to small implantable medical devices, such as stents. Due to the viscosity of polymers during coating, it is difficult to evenly coat a medical device to faithfully replicate its form. Fifth, polymeric coatings are large and bulky relative to their bioactive material storage capacity. Sixth, when delivering a bioactive material to a patient over a longer time period, the bioactive material needs to be stabilized. Some polymeric coatings can not provide a stable storage environment for the bioactive material, in particular when liquid, such as blood, is able to seep into the polymeric coating. Seventh, polymeric coatings, which by their nature have large pores, can protect microorganisms in the interstices of the polymeric coating, thus increasing the risk of infection. Finally, polymeric coatings remain on the medical device once the bioactive materials they contained have fully-eluted. Thus, the negative effects of the polymeric coating remain even after the bioactive materials are no longer providing continued treatment.
Sintered metallic structures can be used as an alternative to polymeric coatings. In a typical sintering process, small particles of metal are joined by an epoxy and then treated with heat and/or pressure to weld them together and to the substrate. A porous metallic structure has then been created. While effective in some instances, sintered metallic structures have relatively large pores. When a bioactive material is loaded into the pores of a sintered metallic structure, the larger pore size can cause the biologically active material to be released too quickly. As noted above, it would be desirable to have the ability to increase the bioactive material storage capacity in a bioactive composite material so that, for example, the bioactive material can be released to a patient over a long period of time.
While several alternative methods for coating stents and other implantable medical devices with bioactive materials have also been proposed, these methods also suffer from drawbacks including those resulting from processing limitations in relation to the underlying substrate or bioactive agent to be coated; inability to obtain even distribution of coatings or bioactive materials; problems with adhesion; biocompatibility issues (e.g. toxicity, or other adverse biological response); complexity of processing; size; density (and thus volume of drug that can be held and released); timing of drug release; high electrical impedance; low radiopacity; or an impact of the coating on the underlying substrate's intended function (e.g. mechanical properties, expansion characteristics, electrical surface conduction, radiopacity, etc.). Thus, notwithstanding certain benefits that may be provided by polymeric coatings, sintering or other alternative methods for coating implantable medical devices with bioactive materials, there is still room for improvement. Specifically, it would be beneficial if a coating process and matrix could be provided that overcomes one or more of the above-mentioned limitations.